POS1386 THE OCCURRENCE OF INFUSION-RELATED REACTIONS TO RITUXIMAB IS ASSOCIATED WITH LOW PLASMA LEVELS OF MYELOPEROXIDASE-DNA COMPLEXES.
Authors: C. H. Lu, T. J. Lee, C. L. Yu, S. C. Hsieh
Journal: Annals of the Rheumatic Diseases (2022)

Background Rituximab (RTX), a chimeric anti-CD20 antibody, is used in the treatment of rheumatic diseases. Infusion-related reactions (IRRs) are the most common adverse event, and premedication may reduce the incidence [1]. To date, there is still no effective predictor for the occurrence of IRRs. Objectives To identify factors predicting the occurrence of IRRs during the first course of RTX therapy in patients with rheumatic diseases. Methods We prospectively enrolled 29 patients with rheumatic diseases underwent the first course of RTX infusion, which consisted of two 500-mg intravenous infusions separated by about 2 weeks. Each patient received 100 mg intravenous methylprednisolone 60 minutes prior to each RTX infusion. Complete blood counts and C-reactive protein tests were performed before each infusion. The plasma levels of IL-1β, IL-6, IL-8, TNF-α, B-cell activating factor (BAFF) and plasma levels of myeloperoxidase (MPO)-DNA complexes were measured. All-grade IRRs occurring within 24 hours after infusions were recorded. Mann-Whitney U test was conducted to analyze factors associated with IRRs. Results The demographics and characteristics of the patients were shown in Table 1. Two patients reported IRRs in the first infusion, and three patients had IRRs in the second infusion of the first course. Among the five IRRs, four were skin rashes and one was headache. No serious events were found. A significant association between the low levels of MPO-DNA complexes and IRRs in the second infusion was noted ( p = 0.011). The low plasma levels of MPO-DNA complexes also tended to be associated with the occurrence of IRR in the first infusion. The IRRs were not significantly correlate with absolute neutrophil counts, absolute lymphocyte counts, and the plasma levels of IL-1β, IL-6, IL-8, TNF-α, and BAFF. Table 1. The characteristics of the patients received the first course of RTX treatment (n = 29). Age (years) ‡ 44.9 (38.4 to 50.9) Gender, female (%) 26 (89.7) Diagnosis Antiphospholipid syndrome, n (%) 11 (37.9) Autoimmune thyroid disease, n (%) 6 (20.7) Sjögren’s syndrome, n (%) 4 (13.8) Systemic lupus erythematosus, n (%) 2 (6.9) Rheumatoid arthritis, n (%) 1 (3.4) Others, n (%) # 5 (17.2) Blood test during each infusion Before first infusion Before second infusion MPO-DNA complexes levels ‡¶ 11% (3% to 53%) 15% (3% to 32%) IL-6 (pg/mL) ‡ 8.3 (6.9 to 11.2) 12.1 (8.5 to 13.8) IL-8 (pg/mL) ‡ 14.4 (12.6 to 15.9) 13.0 (12.1 to 14.9) TNF-α (pg/mL) ‡ 8.9 (6.9 to 12.7) 8.1 (6.1 to 11.2) BAFF (pg/mL) ‡ 155.1 (121.3 to 231.9) 276.8 (201.3 to 331.2) IL-6 (pg/mL) ‡ 8.3 (6.9 to 11.2) 12.1 (8.5 to 13.8) Absolute neutrophil count (/μL) ‡ 4380 (3441 to 5890) 4360 (3286 to 8195) Absolute lymphocyte count (/μL) ‡ 1511 (1198 to 1799) 1214 (854 to 1465) C-reactive protein (mg/dL) ‡ 0.03 (0.01 to 0.10) 0.04 (0.02 to 0.21) ‡ Data are presented in median and interquartile range. # Other diagnoses include systemic sclerosis, dermatomyositis, vasculitis, pemphigus, myasthenia gravis. ¶ Data are presented in ratio to positive control. Conclusion Plasma MPO-DNA complexes represent neutrophil extracellular traps released by activated neutrophils. Neutrophils could be involved in the response to RTX therapy [2]. In this study, the risk of IRRs to RTX tended to increase when the plasma level of MPO-DNA complexes is low. Further research is needed to clarify the impact of activated neutrophils on RTX therapy. References [1]Paul F, Cartron G. Infusion-related reactions to rituximab: frequency, mechanisms and predictors. Expert Rev Clin Immunol. 2019 Apr; 15(4):383-389. [2]Taylor RP, Lindorfer MA. Fcγ-receptor-mediated trogocytosis impacts mAb-based therapies: historical precedence and recent developments. Blood. 2015 Jan 29; 125(5):762-766. Acknowledgements This work was supported by the Ministry of Science and Technology (National Science Council) of Taiwan (Grant No. 109-2314-B-002-234 and 110-2314-B-002-244). Disclosure of Interests None declared